St Jude Looks at Long Term DIPG Survivors

At a poster session for the 3rd biennial Pediatric Neuro-Oncology Basic and Translational Research Conference next month,  physicians from St Jude Research Hospital will be presenting a retrospective review of their patients who had prolonged survival despite being given a diagnosis of diffuse intrinsic pontine glioma.

These physicians reviewed the records of DIPG patients at St Jude from October 1, 192 to May 31, 2011.  Of the 191 patients there were 5 long time survivors with a median time from diagnosis being 9.3 years!    It seems 4 out of 5 of these patients had some atypical clinical or imaging features that put them on the side of potentially better outcomes than the average.

All these survivors underwent neurocognitive testing.  Interestingly, and unfortunately like so many other children who undergo brain radiation, cognitive function was impacted in 4 of 5 patients- two falling in the range of borderline/mild mental retardation.   These findings will become increasingly important when there is better survival statistics for DIPG.

The researcher point out that prolonged survival does not equal cure.   Two of the patients had progression years after their initial treatment with radiation.

It will be interesting to see what comes of this.  Certainly the DIPG Registy could become very important to bring the information on all long term survivors together at one place.   

Reference:
Clinico-radiologic characteristics and neurocognitive assessment of long-term survivors of diffuse intrinsic pontine glioma
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=738281

DIPG- Adults versus Kids

Adult diffuse pontine lesions have a median survival range of 4.9 to 7.3 years!

There seems to be a bimodal type of distribution of diffuse brainstem lesions.  The first peak is generally in the the 4-9 year olds and the second is in the 20-50 year olds.   Like children, diffuse brainstem gliomas are the most frequent type of brainstem tumor in adults.   Unlike children who tend to have high grade lesions with a prognosis on average of about 1 year, young adults with similarly appearing lesions when biopsied are low grade and may have a much greater life expectancy.

 Although adult and pediatric DIPG patients might present with similar symptoms (such as ataxia and cranial nerve palsies), is important to realize that despite potentially similar appearances of the diffuse pontine lesions on MRI this is not the same disease process.   This is made clear in the review (full text link) published last year in The Oncologist.  For those interested the read is not near as difficult as the recent molecular tumor biology publications.   In addition, there are three MRI series of adult patients with diffuse pontine lesions.  One of these survivors' MRIs is shown 10 years out.

 I highly recommend a peak at these MRIs (which is easier to do on pub med if one doesn't want to read the entire publication.)  It is amazing how the MR imaging is so similar to what we see in pediatric patients, yet the course can be so much different.

 No one know yet why the tumors are so different in different ages.

Reference:
Adult Brainstem Glioma
Oncologist. 2012;17(3):388-97. doi: 10.1634/theoncologist.2011-0335. Epub 2012 Mar 1.
Full Free Text
http://theoncologist.alphamedpress.org/content/17/3/388.long

10 and 15 year Survivors

Meet Connor and Tori.

Their names have been around the internet for some time.  I absolutely believe that their parents were told the awful prognosis of DIPG at diagnosis and although I have never seen the MRIs I don't doubt that the lesion in these children's brains were diffuse and intrinsic and pontine.

Connor was just 5 weeks old when he was diagnosed with a DIBSG (diffuse intrinsic branstem glioma).  The parents knew something wasn't right about a week earlier when he wasn't latching on and seemed exhausted.   A seizure sent him to Cincinnati Children's ER.   During the admission for failure to thrive a golfball size tumor was found in his brainstem.   At that young age there were no therapeutic options.  He was sent home with a feeding tube to die.  In those first  two years he had spectroscopy scans which showed high levels of choline and other cancerous indications but it didn't change.   As far as I can tell his last MRI still had residual tumor at age 2.  In September, this happy healthy boy will have his 10 year anniversary from diagnosis.    His mom has a caringbridge site to give hope to other DIPG parents.

Tori seems like a regular teenage girl.   However, not long after she was born that thought that we would ever know seemed beyond impossible.  Tori was born in June 1998 and a few weeks later was found to have some typical DIPG symptoms.   Her eyes had trouble tracking and the side of her face seemed stiff.  AN MRI showed a brainstem glioma (that is what they all were called at that time).  The doctors told her parents she would die.   With no conventional options, they searched for alternatives.  This year she wrote her own update.  This fall will be 15 years since diagnosis for her!

One can ask a million times but no one knows why these children have survived.  What we do know is that there have been other cases of spontaneous regression of diffuse pontine lesions in neonates.   It has been reported in the literature before.

A case from Germany is remarkable similar to the two above.  A 7 week old infant was found to have an MRI "strongly suggestive of diffuse pontine glioma".  By 27 months the lesion was gone.

A slightly different situation (also from Germany) is the first reported case of spontaneous remission that I am aware of.   A 2-year-old boy was found to have a large, diffuse pontine tumor extending into the midbrain.   A biopsy showed a fibrillary astrocytoma.   He received a shunt but no other conventional therapy.   By the age of 6.6 years the tumor was no longer visible on imaging.

In 2005, two US neurosurgeons reported two cases of spontaneous regression of diffuse brainstem lesions in neonates.  These two newborns were found to have limb weakness and cranial nerve abnormalies.  MRIs in the first week after birth revealed a large pontomedullary tumor.  Neither child received conventional treatment.   The authors related that the children were normal at age 4 and 10.

A followup letter to the editor to the above case report came from Texas Children's relating a similar story although the child presented at 11 weeks of age.   At the time of publication she was 12.

These authors stressed that nearly all patients with diffuse brainstem lesions do poorly-  including neonates.   In 2008 Sick Kids published a case report on  two infants with "large, expansive, non-enhancing, intrinsic pontine masses diagnosed as DIPGs.   They were treated only with supportive care and died by 2 weeks of age.   One of the children underwent autopsy and was found to have a brainstem PNET.

We have no idea how often this happens.  This is why the DIPG Registry  is critical in understanding this disease.  Both families and physicians can enroll patients including children who have died.

The bottom line is:  1) we really don't understand DIPGs, and 2) there are children who have been diagnosed with DIPGs-based on the incomplete knowledge that we currently have- who truly have had spontaneous regression of their tumors and 3) most of the children with report spontaneous regression have been very young.

French DIPG Site- Tumeur du Tronc Cérébral

Prior to the past decade or so it has been virtually impossible to truly connect DIPG famililes as a community in any significant way.   The internet has changed all that.  Not only is there virtually instantaneous communication- but that communication can happen even if the languages are different!

It might not be easy to find these sites at first; however, if one translates brainstem glioma or pontine glioma (in a translator site such as google translator) some time new worlds open up.  This is exactly what I did in French.   Putting "Tumeur du Tronc Cérébral" in the search engine was immediately rewarded by finding another DIPG site from halfway around the world.  Fortunately (for me) my commuter asked me immediately if I wanted to read in English.

 http://www.tumeurtronccerebral.com/

Funny, smart, sensitive Eva inspired her parents to make this site.  This little girl subsequent to developing a squint was diagnosed on June 5, 2010.  After a 7 1/2 month battle she died on January 20,2010.  

This site contains quite a bit of information- from understanding high and low grade brain stem tumors to different therapy options.   As with many parents starting sites, there are items trying to make a difference.   One such thing is a petition calling on more research for pediatric cancer research in France.  Another is a survey of parents who have had children with DIPG.   

Perhaps one of the most sought after items is a page about long term survivors.

http://www.tumeurtronccerebral.com/longs-survivants__15_.html

Most of these children are atypical in some way.  There are three points to that:

1) Prolonged survival does not mean a cure- just that so far these children have beaten the statistical odds.   Most of these children's site that have information about the tumor show that it is still there.

2) Not all families that came into the DIPG world are dealing with typical DIPGs so these rare but hope-giving kids are particularly important to those dealing with atypical DIPG.   

3) At least one child listed there is known to be typical by current standards- Dasia.

DIPG happens all around the world.   The world wide web is making all the difference in our being able to communicate and understand what is going on internationally.

Note- to understand the difference between typical and atypical DIPGs

http://dipg.blogspot.com/2013/03/typical-versus-atypical-what-does-that.html

Case Report- Two Children with Prolonged Survival

During time period between June 2008 and June 2009, Children’s Healthcare of Atlanta treated three children diagnosed with DIPG with radiation followed by temozolomide and avastin.   Two children were still alive at 37 and 47 months from diagnosis.  The other child had progression free survival for 12 months followed by rapid deterioration with death at 14 months from diagnosis. 

Here is the recent case report of these two children who have surpassed the 3-year mark since diagnosis of a DIPG and were still going strong at the time of publication.

Patient 1- was described as an 11-year-old male with a 2 month history of weakness on the left side as well as walking and swallowing difficulties.   The initial MRI showed a 4cmx3.5cmx3cm non-enhancing tumor of the pons and medulla.  

Patient 2-was described as an asymptomatic 7-year-old female who was found to incidentally have a 3cmx2.3cmx2.6cm pontine mass after head trauma.   She was observed closely with serial MRIs.  Two MRIs showed increased tumor size and at 8 months from initial presentation she deteriorated developing a facial palsy, right sided weakness and hydrocephalus.  The tumor was 4.2cmx4.3x3.8cm with new focal areas of enhancement.

The children were treated with temozolomide 200mg/2d/d for 5 days ever 28 days and avastin 10mg.kg.dose every 14 days.   In both patients a 65% decrease in tumor size was seen.   No steroids were needed after 10 weeks from radiation.   The therapy was tolerated well.  At publication both children were doing well and continuing on treatment.  The paper notes that the boy was going to school and playing soccer at 37 months.  

 (Note- the actual paper has several MRI images provided both initially and later for both children.)

The authors speculate that the combination of temozolomide and avastin might deliver more temozolamide to the tumor because avastin might normalize the tumor vasculature.    As support for this theory the authors point to cilengtide altering perfusion which allowed for increased temozolamide delivery  for gliomas.    Perhaps avastin has a similar effect.

An additional advantage of this combination might be the decreased need for steroids.

The authors recommend consideration of an expanded DIPG clinical trial with this combination.

By the way, the female child appears to be atypical both in presentation and focality in her tumor.   On the other hand, the male child seems to have a very typical presentation for DIPG.

Reference:

Prolonged survival after treatment of diffuse intrinsic pontine glioma with radiation, temozolamide, and bevacizumab: report of 2 cases.

J Pediatr Hematol Oncol. 2013 Jan;35(1):e42-6.

http://www.ncbi.nlm.nih.gov/pubmed/23249962